少突胶质前体细胞在神经发育及疾病中的作用

The Role of Oligodendrocyte Precursor Cells in Neurodevelopment and Disease

少突胶质前体细胞(oligodendrocyte precursor cell,OPC)是中枢神经系统(central nervous system,CNS)中普遍存在的胶质细胞,参与维持正常神经功能并在多种疾病中发挥重要作用。OPC功能异常在多种疾病中均有观察,包括多发性硬化症、阿尔茨海默病、帕金森病以及精神障碍。这些细胞不仅可以分化为少突胶质细胞(oligodendrocyte,OL),形成髓鞘,发挥保护轴突和加速电信号传导等关键作用,还参与调节神经发育、神经环路形成以及神经可塑性,对环境因素做出响应,与神经系统疾病密切相关。OPC同时呈现显著的异质性,受到发育程序、刺激特异性的细胞反应、CNS位置、细胞间相互作用和其他调控机制的影响。本文全面综述了OPC的起源、增殖、迁移、分化等多个方面,以及其在神经发育和神经系统疾病中的关键作用。深入了解OPC的生物学功能和临床意义有助于更好地理解神经系统发育及其疾病机制,为神经系统疾病的治疗提供新的思路和策略。

Oligodendrocyte precursor cells(OPCs)represent the fourth major cell type within the central nervous system(CNS),ubiquitous beyond neurons,astrocytes,and microglia,constituting 5%-8%of the total cell population.They exhibit widespread distribution throughout the central nervous system,including brain,spinal cord,and optic nerve.OPCs showcase distinct protein expression,featuring platelet-derived growth factor receptor alpha(PDGFRα),neural/glial antigen 2(NG2),SRY-related HMG-box protein 10(Sox10),and oligodendrocyte transcription factor 2(Olig2),endowing them with robust proliferation and migration capabilities.This capacity persists into adulthood and even later stages,contributing to the maintenance of normal neurological functions such as learning,memory,and sleep,while playing crucial roles in various neurological disorders.OPCs also display significant heterogeneity,influenced by developmental programs,stimulus-specific cellular responses,CNS locations,cell-cell interactions,and other regulatory mechanisms.Dysregulation of OPC function has been observed in various diseases,including multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Pelizaeus-Merzbacher disease,as well as psychiatric disorders such as schizophrenia,depression,emotional disorders,and autism spectrum disorders.In addition to differentiating into oligodendrocytes to form myelin sheaths and supporting axonal protection,fast signal transmission,and metabolic support,OPCs actively participate in regulating neural development,circuit formation,and neural plasticity.They respond to environmental factors and are closely associated with neurological disorders.This comprehensive exploration of OPCs delves into their development,functional diversity,and associations with neurological disorders.Firstly,the article introduces the complex regulatory mechanisms of OPCs during embryonic development,encompassing transcription factors,chromatin regulatory factors,post-translational modifications of proteins,microRNA,and intercellular communication,emphasizing their significance in the nervous system.Subsequently,it reviews recent research findings on various functions of OPCs,not only in neuronal development,phagocytosis,and reshaping activities,but also involving their secretion of factors,interactions with surrounding blood vessels,and regulation of inflammatory responses.Furthermore,the review highlights the connections between OPCs and neurodegenerative diseases(such as Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis)and psychiatric disorders(such as schizophrenia and depression),indicating their potential roles in disease occurrence and progression.The review then explores emerging trends in OPC research,addressing the evolving understanding of their roles in neurological health and disease.Recent studies have unveiled novel aspects of OPC functionality,shedding light on their ability to modulate immune responses,interact with the extracellular matrix,and contribute to neurovascular coupling.Additionally,insights into the role of OPCs in neuroinflammation and the crosstalk between OPCs and neurons have expanded our comprehension of their impact on neural circuits and plasticity.In conclusion,the comprehensive review summarizes the current understanding of OPC functional impairments and discusses future research directions.Emphasizing the importance of in-depth analysis of OPC heterogeneity and their roles in the development,repair,and diseases of the nervous system,this review not only provides profound insights into the multifaceted functions of OPCs in the nervous system but also sets the stage for future investigations into the intricate interplay between OPCs and the broader neural environment.With an expanded scope encompassing recent advances and emerging research trends,this review contributes to the ongoing dialogue in the field of neuroscience,fostering a deeper understanding of OPC biology and its implications for therapeutic interventions in neurological disorders.